The respiratory tract is one of the main interfaces between the body and the environment. Its major structural components are designed to maximize gas exchange and provide sensory input (i.e. odor detection). As such, the respiratory tract can become a target for a broad range of airborne environmental agents contributing to an expansive array of human diseases. Alterations in the structure or function of the respiratory system by diseases can dramatically affect the interface with the environment and alter the quality of life. To improve our ability to predict the dosimetry and thus the consequences of airborne pollutants (gases, vapors, particulates or atmospheric releases of chemical/biological weapons) or drugs intentionally administered by inhalation for normal or potentially sensitive populations, 3-dimensional (3D), biologically based models of the respiratory tracts of animals and humans will be developed by a cross-disciplinary team of mathematicians, physicists, chemists, and biologists. The overall specific aims of this partnership are to: (1) develop and apply magnetic resonance imaging and fluorescent microsphere techniques to determine the dynamic, 3D structural and functional properties of the respiratory tract; (2) determine the 3D cellular organization and metabolic capacity; (3) develop and extend software and computational capabilities for 3D modeling and upscaling techniques for cellular-to-organ model integration; (4) develop a normalized atlas of rat geometries with explicit measures of variability; (5) conduct in vivo gas exchange and particulate dosimetry studies for model validation and identification of model uncertainties; and (6) provide a web-based "pulmonary physiome" platform for dissemination and training of researchers and clinicians in the use of imaging and annotated model databases. Five projects are designed to provide the necessary data on the dynamic structure and function of the respiratory system for the development and validation of the computational models. To support these five projects, three technology development cores will be established in advanced imaging, computation, and database/modeling access and training for external users. A fourth core will serve as an administrative interface and will provide statistical support among the participating institutions and projects.